The application of modern molecular biological and genetic techniques to the study of acquired and inherited human diseases has provided new insights into the role of ion channel mutations in a wide variety of human diseases (ion channelopathies). Although defects in anion (chloride) channels have been definitively linked to human diseases such as cystic fibrosis, generalized myotonias, Batter Syndrome and recessive nephrolithiasis, the possible role of ion channelopathies in cardiovascular disease has been mostly limited to the consideration of cation channel defects, and the role of anion channels in many types of cardiovascular disease has not yet been systematically investigated. The long term objective of this Center of Biomedical Research Excellence (COBRE) application is to advance our present understanding of the molecular and biophysical properties of anion channels and their regulation in the cardiovascular system, and determine their role in human cardiovascular disease, using complementary experimental approaches that include well- defined animal disease models, transgenic mice, and human molecular genetics. The proposed COBRE represents a comprehensive, multi- disciplinary effort involving the coordination and integration of five separate, but closely related, research projects, supported by three core facilities. This COBRE program offers a variety of unique opportunities: (1) to advance knowledge regarding the role of anion channelopathies in cardiovascular disease, (2) to support and promote the development of a cadre of young biomedical research investigators at the University of Nevada, (3) to promote the expansion of an existing, unique, NIH-funded biomedical research program, and (4) to promote the development of new, state-of-the-art transgenic, genomic and molecular genetic resources at the University of Nevada School of Medicine.